SUMMARY1. Monoclonal antibodies (mAbs) of high specificity and stability have become key resources in the therapeutic, diagnostic and drug discovery fields to treat various immunological disorders and malignancies of different organs.2. The latest genetic engineering technology applied in antibody design and production, such as phage display technology and genetically modified mouse, have revolutionized the clinical applicability and feasibility of the use of mAbs in humans.3. Innovative antibody products in the forms of single-chain or super-humanized antibody therapeutics having a higher affinity for target antigens and minimal antigenicity in hosts have been introduced for experimental purposes and/or clinical trials.4. Although there are successful examples of antibody therapeutics in the market, the use of mAbs in treating hepatitisrelated disease and hepatocellular carcinoma is rare and remains to be exploited.
1. Tripterygium wilfordii (TW) contains bioactive compounds that possess immunosuppressive properties. These compounds are considered to be potential drugs in the treatment of acute graft rejections. However, their structure-activity relationships remain unknown. 2. The aim of the present study was to delineate the molecular moieties of triptolide that could account for its ability to inhibit inflammatory responses. In this context, purified TW active compounds (triptolide and triptonide) and synthetic triptolide derivatives were prepared to investigate the structure-activity relationships of triptolide. To this end, rat splenocytes were treated with increasing concentrations of the compounds and then allogenically stimulated using a mixed lymphocyte reaction to determine their antiproliferative activities. From the results, the IC50 value of each compound was calculated. 3. Modification of the beta-hydroxyl group at the C-14 position of the triptolide molecule significantly affected the immunosuppressive activity of T59, as demonstrated by a sevenfold increase of the IC50. Conversely, reduction of the gamma-butyrolactone group in T60 and T61 completely abrogated the antiproliferative effect. Alterations in the C-14 beta-hydroxyl and gamma-butyrolactone groups also resulted in reduced cytotoxicity. 4. The present findings demonstrate that the C-14 beta-hydroxyl and gamma-butyrolactone moieties of the triptolide molecule are crucial for its anti-inflammatory properties and cytotoxicity and are responsible for the compound's antiproliferative activity.
Bacterial endotoxin [e.g. lipopolysaccharide (LPS)] can trigger systemic hyper-inflammatory that subsequently leads to multiple organ failure and lethality (gram-negative sepsis). This paper describes the development of endotoxin-neutralizing peptides that potentially treat sepsis. These peptides have been derived from bactericidal/permeability-increasing protein (BPIP), anti-microbial peptides, and leukocyte CD18 antigen and some of these peptides have been tested in clinical studies.
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